The biggest negative effect would be disease. Ninety percent of native Americans were wiped out by smallpox, diphtheria, whooping cough, and plague. Europeans, while not entirely immune, had some resistance. Natives, on the other hand, had never experienced these diseases and died in droves as a result as they did not know how to ease the symptoms, let alone treat the illness. Smallpox enabled Cortes to take the Aztec empire and it depopulated New England before the Pilgrims arrived in 1620. Diseases spread all over the North American continent due to the extensive trade networks between tribes that have only recently been noticed by contemporary historians. Another negative effect would be the influx of non-native animals to native biomes. Pigs especially were bad because they rooted through native cropland that was not fenced. Since it was not fenced, Europeans would not acknowledge that it was planted intentionally and would not compensate the natives for their losses. This led to conflict and eventually skirmishes between colonist and native.
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