I would go with harvests failing and a bunch of civil war and seiges. All sorts of things that make people starve and turn violent. Cannabalism becomes a real issue and people that partake all turn mad and start having dreams that lead them to Yeenoghu worship.
Later in the campaign, a disease like in 28 days later emerges. People go feral and hunt their fellow humans down in packs.
The ghoul king (Doresain) decides that famine and cannabalism are his domain, so he tries to start up a bunch of cults too. Sometimes trying to steal influence from Y.
The wilds and farmlands are overrun by gnolls, ghouls and madmen. The survivors huddle in cities that are starved then overrun one by one until only the port cities remain, being less dependant upon the farmlands. Then the Saughain appear, promised rich spoils by Y. Maybe they can be dealt with, intimidate or interrogated to tell the PCs about the emmisary of Y that came to them, a human they once trusted. The PCs capture the emmisary and boasts about the BBEG-plan, leading to the final confrontation in this realm.
From there the PCs are sucked through the portal meant to release Y. They are trapped on the wrong side and now (being high level) they must fight through his domain (maybe with the help of Baphomet and the Ghoul King who are rivals) and confront him before his plans wipe out the last of humanity.