PHILADELPHIA - Pope Francis kicked off the final leg of his historic trip to the United States on Saturday with a Mass at Philadelphia's most sacred shrine, saluting priests, nuns and other Catholics for going to the "peripheries" of society to help the downtrodden.

He also called for women and young people to play a significant part in strengthening the church.

"This morning I learned something about the history of this beautiful cathedral: the story behind its high walls and windows," the pope said at a packed Cathedral Basilica of Saints Peter and Paul. "I would like to think, though, that the history of the Church in this city and state is really a story not about building walls, but about breaking them down.

See alsoComplete coverageInteractiveYour messages to the popeSee alsoPope's visit: Follow along at News 12

"It is a story about generation after generation of committed Catholics going out to the peripheries, and building communities of worship, education, charity and service to the larger society," he said.

The two-day visit to Philadelphia follows memorable stops in New York and Washington, D.C., two cities transfixed by the presence of the first pontiff from Latin America and the first Jesuit pope.

Francis departed from Kennedy Airport shortly after 9 a.m. as priests, nuns and parishioners bid him farewell. Among them was Bishop William Murphy of the Diocese of Rockville Centre.

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The U.S. visit is to culminate with a massive outdoor Mass on Sunday on Benjamin Franklin Parkway that is expected to attract 1 million people.

In his homily Saturday morning, Francis praised "the efforts of all those dedicated priests, religious and laity who for over two centuries have ministered to the spiritual needs of the poor, the immigrant, the sick and those in prison.

"And it is seen in the hundreds of schools where religious brothers and sisters trained children to read and write, to love God and neighbor, and to contribute as good citizens to the life of American society."

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He singled out Saint Katharine Drexel, a Philadelphia native he described as "one of the great saints raised up by this local Church."

He left followers with the repeated message "y tu" -- "What about you?" -- and asked the faithful how they plan to respond "to the Lord's call to build up his Body, the Church."

Drexel had received that pointed question from Pope Leo XIII as a young laywoman, according to Francis. The words "made her think of the immense work that had to be done, and to realize that she was being called to do her part."

One of the challenges facing the church in this generation, Francis continued, is the need for its followers to develop "a sense of personal responsibility for the church's mission, and to enable them to fulfill that responsibility as missionary disciples."

The pontiff said the rapidly changing society calls for "a much more active engagement on the part of the laity" -- specifically, he said, "valuing the immense contribution which women, lay and [the] religious, have made and continue to make in the life of our communities."

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Francis has repeatedly referred to the strengths of religious women during his United States tour, and his vocal appreciation of their hard work was felt personally by Sister Anita Bolton, whose order of nuns, the Sisters of the Holy Redeemer, work in health care.

"It's a thrill to be here. It's a once-in-a-lifetime experience to witness the presence of the Holy Father," Bolton said. "His message of love, of kindness, of mercy and of compassion -- he walks the walk."

She said she was especially moved by Francis' recent statement of support for nuns in the United States, who had been under a Vatican investigation for allegedly emphasizing social justice issues over traditional church doctrine on topics such as abortion.

This year, Francis ended the investigation, which started under his predecessor, Pope Benedict XVI. Francis has stated he "loves" the nuns.

"It was beautiful," Bolton said. "We love him, too -- it's mutual."

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Toward the end of the Mass, Archbishop Charles Chaput of Philadelphia welcomed Francis to the City of Brotherly Love -- which, he said, has waited a long time for his arrival.

"This is a city that would change its name to 'Francisville' today if we could do that without inconveniencing the rest of North America," Chaput said. "So we welcome you with all our hearts, and a huge amount of enthusiasm and joy."

As in all his appearances in the United States, many who saw Francis in person were overcome with emotion.

Neilson Carlin, who said he painted the picture of Jesus, Mary and Joseph that adorns the altar, said he was overwhelmed -- especially when the pope stopped before his painting.

"The pope is fantastic. He's a great leader at a crucial time," said Carlin, of Kennett Square, Pennsylvania. He attended the Mass with his family. As the pope paused in front of his painting, Carlin's eyes filled with tears.