Human head and body lice are obligatory hematophagous ectoparasites that belong to a single species Pediculus humanus. Only body lice, however, are vectors of the infections gram-negative bacteria Bartonella quintana. Due to their near identical genomes, yet differential vector competency, head and body lice provide an ideal model system to study an insects ability to gain or lose vector competency. Using our in vitro louse rearing system, we have infected both head and body lice with a blood containing B. quintana in order to detect differences in B. quintana proliferation between head and body lice as well as transcriptional regulation of immune-related genes. B. quintana proliferates rapidly in body lice after 6 days post-infection, but declines in head lice after 4 days post-infection, possibly explaining, in part, the differential vector competence between the two insects. A transcriptome analysis using whole lice followed by qPCR verification of head and body lice immune-related genes was then conducted using uninfected, versus B. quintana infected lice to identify potential genes involved in vector competence. The immune-related genes Defensin 1, Fibrinogen-related protein and Spaetzle, were differentially regulated between head and body lice and were identified as potential targets for future research. Previously studied immune-related genes, PGRP, Defensin 1 and Defensin 2 transcription levels were also assessed in body louse midgut using qPCR following B. quintana infection. In this case, B. quintana infection did not result in significant effects on the transcript levels of these genes in midgut tissue. Overall transcriptional profiles of head and body lice genomes were notably different, including difference in the expression of 18.3 % of immune related genes, a finding that strongly supports the contention that immune system differences between head and body lice are the primary reason for difference in vector capacity.