Short rotation woody biomass cultivars developed from fast-growing shrub species of willow (Salix spp.) have superior properties as perennial energy crops for the Northeast and Midwest US. However, the insect pest potato leafhopper (PLH) Empoasca fabae (Harris) can cause serious damage and reduce yield of susceptible genotypes. Currently, the willow cultivars in use display varying levels of susceptibility under PLH infestation. However, genes and markers for resistance to PLH are not yet available for marker-assisted selection in breeding. In this study, transcriptome differences between a resistant genotype 94006 (S. purpurea) and a susceptible cultivar 'Jorr' (S. viminalis), and their hybrid progeny were determined. Over 600 million RNA-Seq reads were generated and mapped to the Salix purpurea reference transcriptome. Gene expression analyses revealed the unique defense mechanism in resistant genotype 94006 that involves PLH-induced secondary cell wall modification. In the susceptible genotypes, genes involved in programed cell death were highly expressed, explaining the necrosis symptoms after PLH feeding. Overall, the discovery of resistance genes and defense mechanisms provides new resources for shrub willow breeding and research in the future.