Well. The best answer is that they didn't have immunities to the things that had been killing white people for centuries like Flus, Colds and smallpox and the Black Plague.
So, when white trappers first came to trade with native Americans within a few months up to 90% of them were dead from plagues and smallpox and flus and colds because they had no natural immunity because they had never lived with thousands or millions of people in cities in Europe like White people had. If you study how many people died in Europe between the Time of Christ and about 1500 or 1600 anyone without immunities had already died hundreds of years before in Europe. But, native Americans hadn't lived in unclean city environments without sanitary sewage like we have today where water often was polluted with sewage. So, people from childhood drank beer because water might kill you in Europe if you lived in the cities. So, they didn't have the immunities that those who had survived and were white and moved to North America had. So, up to 90% or more of native Americans died whenever they first saw or touched white people within 3 to 6 months here in the U.S. Most native people went to the bathroom in moving rivers rather than bury their urine and feces and so they could wash off in rivers. In Europe this might have been true for the common folk too. But, because of the numbers of people in Europe this often caused many people to get sick and die because of so many polluting the water in the cities. And this caused plagues. Also rats carried plagues too which found grain and food especially in cities. So, European cities (at least for the lower classes were always death traps) until the 1800s and 1900s generally speaking when sanitation started to be practiced by city dwellers starting from the upper classes and slowly working down to the lower classes over time through education.
For example, in the 1840s around the Gold Rush there was at one point a dead Indian in California leaning against every oak tree from San Francisco to Sacramento. If you have ever driven north from say San Diego north to Redding you will see thousands of Oak trees especially growing wild in the valleys and lower hills of California. This is documented by witnesses at the time All the dead native Americans leaning against oak trees. I think they either died of Smallpox or plague of some kind that they got from the Gold Miners. Dying leaning against an Oak Tree was the route to Heaven for them at the time. This was traditional for Native Americans living in California when they knew they were dying or they wanted to be healed the trees would often heal them or take their pain and they knew to do this. This is a part of the natural symbiosis between trees and humans going back thousands of years in California Native American traditions.
Did you mean: when did plague kill of many California indians?
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Untold History: The Survival of California's Indians | KCET
https://www.kcet.org/shows/tending.../untold-history-the-survival-of-californias-india...
Sep 26, 2016 - Finally, in 1911, Ishi, the last wild California Indian, wandered out of the ... deserts likely protected California Indians from the plagues that had ravaged .... Many of the Wintu were killed where they stood, first with rifle fire, then ...
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