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Baltimore is the largest city in the U.S. state of Maryland, and the 30th-most populous city in the United States. With a population of 621,849 in 2015, Baltimore is the largest independent city in the United States. As of 2016, the population of the Baltimore metropolitan area was estimated to be just under 2.8 million, making it the 21st largest metropolitan area in the country. Baltimore is also part of the Washington-Baltimore combined statistical area (CSA), the fourth largest CSA in the nation with a calculated 2016 population of 9,665,892. Founded in 1729, Baltimore is the second-largest seaport in the Mid-Atlantic. The city's Inner Harbor was once the second leading port of entry for immigrants to the United States and a major manufacturing center. After a decline in major manufacturing, industrialization, and rail transportation, Baltimore shifted to a service-oriented economy, with Johns Hopkins Hospital (founded 1889) and Johns Hopkins University(founded 1876), now the city's top two employers.