, , and humans have distinct transcriptomic responses to larval bites.

ticks are an important vector for at least seven tick-borne human pathogens, including a North American Lyme disease spirochete, . The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural host , a non-natural rodent host, (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite sites. We also note that bite sites on BALB/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval and and, in addition, expand our overall understanding of feeding.