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Horses and donkeys can mate, but they produce a mule, which is always a sterile animal. This means that they cannot produce viable offspring and are (reproductively)(geographically)temporally)behaviorally) isolated.

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User Jeewes
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1 Answer

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Reproductively since they cannot have children, or behaviorally since they cannot mate, which is in their behavioral nature
User Waleed Asender
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