Horseshoe crab blood began to be used to test for the presence of bacterial toxins in vaccines in the 1960s. Soon, it developed into a major industry, but with a devastating impact on horseshoe crab populations.
https://www.npr.org/2023/06/10/1180761446/coastal-biomedical-labs-are-bleeding-more-horseshoe-crabs-with-little-accountabi
The good news is that there is evidence that prehistoric ancestors of the crabs were able to adapt to freshwater a few times. Wikipedia says:
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Only four species of horseshoe crab are extant today. Most are marine, though the mangrove horseshoe crab is often found in brackish water. Additionally, certain extinct species transitioned to living in freshwater. Horseshoe crabs primarily live at the water's bottom but they can swim if needed. In the modern day, their distribution is limited, only found along the east coasts of North America and South Asia.
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Horseshoe crabs are often caught for their blood, which contains Limulus amebocyte lysate, a chemical used to detect bacterial endotoxins. Additionally, the animals are used as fishing bait in the United States and eaten as a delicacy in some parts of Asia. In recent years, horseshoe crabs have experienced a population decline. This is mainly due to coastal habitat destruction and overharvesting. To ensure their continued existence, many areas have enacted regulations on harvesting and established captive breeding programs.
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Perhaps marine horseshoe crabs can be conditioned to live in freshwater just as the lionfish was in this experiment:
Sixth grader credited with scientific breakthrough on lionfish
https://www.youtube.com/watch?v=bJZz9SM2Q8I
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