The college sitcom was recently renewed for a fourth season by NBC, though the network's entertainment president Bob Greenblatt admitted this week that he is "not sure" if Harmon will remain in charge.
McHale, who plays Jeff Winger in Community, has now admitted that it would feel "weird" and "pretty crazy" to continue the show without Harmon.
"Dan's the creator of the show, so to lose his voice would be pretty crazy," he told TV Line. "He gave me the role of a lifetime, so it would be a very weird scenario [to continue] without him.
"I pray that it works out well. That sounds weird and vague, but I really do. I literally am praying."
Rumours that Harmon may quit Community have lingered since his feud with cast member Chevy Chase was made public.
However, Harmon insisted earlier this month that he would not leave the show over Chase, writing on Twitter: "If I 'didn't come back', it wouldn't be because Chevy's a pr*ck. That'd be like punching a wall because water's wet."
Community has been moved to a Friday night 'graveyard' slot for its fourth season in the fall, though Greenblatt has asserted that the show will "survive wherever it goes".
Watch part one of three-part animated Community webisode 'Abed's Master Key' below: