The encounter with the Covenant and Floods where the first that mankind ever had with aliens,which explain the furious xenocidal nature of the Imperium(hey,maybe,just maybe,if the Imperium had nice first contacts with aliens,it might have turned out to be The Federation
Eventually the Ai rebels and leads an army of Iron men
to destroy mankind,which also fits in 40k continuity.
The Spartans where the ancestors of the Space Marine program.
The Great Northern Threadkill.