After twilight and spike traveled to the dragon lands for the dragon games, they would find an odd glowing mushroom and take it back to ponyville to study. Once in the lab of twilight's castle twilit would study the effects of the fungus noting that it was parasitic in nature and wrote letters to Princess Celestia and luna about it, one night spike snuck into twilight's lab and ate the mushroom out of hunger. weeks went by as an outbreak happened after that and half of the mane 6 (pinkie pie, Rainbow dash, Apple jack) and the ponies of equestria were infected, others surviving and doing what they can to survive.

it is unknown if other species such as changelings, Hippogriffs/hippocampus, griffins, yaks, crystal ponies bat ponies, animals and other creatures survived the infection

and now here you are, among the ruins of the crystal empire in the northern regions of equestria, will you find the remaining mane 6 members and other survivors along your journey through equestria or well you end up like many of the twisted infected now roaming the lands