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The result left United, who were reduced to 10 men in the second half, fifth on 61 points, behind Tottenham Hotspur on goal difference, denting their hopes of ending the season in the top four and qualifying for next year's Champions League.
Huddersfield Town were relegated while Manchester United celebrated the full-time managerial appointment of Ole Gunnar Solskjaer with a 2-1 win over Watford.
The 46-year-old Norwegian has guided United to 14 wins in 19 matches in all competitions as caretaker boss since replacing the sacked Jose Mourinho in December.
It was United's first league defeat since December 16.
Paris: Manchester United pulled off one of the greatest comebacks in Champions League history as Marcus Rashford's last-gasp VAR penalty sealed a 3-1 win at Paris St Germain on Wednesday and sent the English side into the quarterfinals on away goals. Never in 106 attempts in Europe's premium club
The result lifted United back into fourth place on 58 points from 29 games, one ahead of fifth-placed Arsenal who were held to a 1-1 draw at Tottenham Hotspur.
The Premier League battle appears a two-horse race after leaders Liverpool and Manchester City both won on Wednesday while Tottenham fell to a second straight defeat.
United had never previously lost at home in European competition by a margin of more than one goal and history suggests their task in the second leg is extremely tough.
The win moves Juergen Klopp's side three points above second-placed Manchester City.
Ole Gunnar Solskjaer got a reality check as his eight-game winning run in all competitions as Manchester United interim manager was ended by Burnley in a 2-2 draw at Old Trafford.