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Lizards and spiders are natural adversaries, yet little is known of adaptations that lizards might possess for dealing with the venomous defences of spider prey. In the Western USA, two lizard species (
Elgaria multicarinata
and
Sceloporus occidentalis
) are sympatric with and predate western black widow spiders (
Latrodectus hesperus
). The consequences of black widow spider venom (BWSV) can be severe, and are well understood for mammals but unknown for reptiles. We evaluated potential resistance to BWSV in the lizards that consume black widows, and a potentially susceptible species (
Uta stansburiana
) known as prey of widows. We investigated BWSV effects on whole-animal performance (sprint) and muscle tissue at two venom doses compared with control injections. Sprint speed was not significantly decreased in
E. multicarinata
or
S. occidentalis
in any treatment, while
U. stansburiana
suffered significant performance reductions in response to BWSV. Furthermore,
E. multicarinata
showed minimal tissue damage and immune response, while
S. occidentalis
and
U. stansburiana
exhibited increased muscle damage and immune system infiltration in response to BWSV. Our data suggest predator–prey relationships between lizards and spiders are complex, possibly leading to physiological and molecular adaptations that allow some lizards to tolerate or overcome the dangerous defences of their arachnid prey.
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