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The main weakness of the Spore is cold damage and biomes. When affected by the cold, Spore Mobs will visibly shiver. If the internal temperature value of the biome is 0.2 or lower, Spore Mobs will be weakened. They also can't spawn in biomes that are cold enough, but that doesn't include the caves beneath the biome.
List of biomes that effect Spore Mobs:
Modded biomes will work if their internal temperature value has been set to be cold enough.
When taking freezing damage, Spore Mobs will receive 5 damage (2.5 hearts) instead of 1. Snowballs will also inflict a freezing effect on Spore Mobs. Additionally, every second, if a Spore Mob is freezing and in a cold enough biome, there is a 5% chance it will receive Slowness II and Weakness for 4 seconds. When having Weakness, all Spore Mobs' Evolution timers will be paused until they no longer have Weakness. Some specific Mobs will have unique ailments when under the affect of the cold.
Linked Mounds at age 4 will be unable to send a Signal to a Proto Hivemind if they are under the effects of the cold.
Spore Mobs can prevent the effects of the cold by huddling together or being under a roof.
Gallery
An Infected Human shivering in a cold biome.