You can use sets:
main_list = list(set(list_2) - set(list_1))
Output:
>>> list_1=["a", "b", "c", "d", "e"]
>>> list_2=["a", "f", "c", "m"]
>>> set(list_2) - set(list_1)
set(['m', 'f'])
>>> list(set(list_2) - set(list_1))
['m', 'f']
Per @JonClements' comment, here is a tidier version:
>>> list_1=["a", "b", "c", "d", "e"]
>>> list_2=["a", "f", "c", "m"]
>>> list(set(list_2).difference(list_1))
['m', 'f']
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