*Article* **Bioinformatic Analysis of** *Ixodes ricinus* **Long Non-Coding RNAs Predicts Their Binding Ability of Host miRNAs**

**José María Medina 1,2 , Muhammad Nadeem Abbas <sup>3</sup> , Chaima Bensaoud <sup>4</sup> , Michael Hackenberg 1,2,\* ,† and Michail Kotsyfakis 4,\* ,†**


**Abstract:** *Ixodes ricinus* ticks are distributed across Europe and are a vector of tick-borne diseases. Although *I. ricinus* transcriptome studies have focused exclusively on protein coding genes, the last decade witnessed a strong increase in long non-coding RNA (lncRNA) research and characterization. Here, we report for the first time an exhaustive analysis of these non-coding molecules in *I. ricinus* based on 131 RNA-seq datasets from three different BioProjects. Using this data, we obtained a consensus set of lncRNAs and showed that lncRNA expression is stable among different studies. While the length distribution of lncRNAs from the individual data sets is biased toward short length values, implying the existence of technical artefacts, the consensus lncRNAs show a more homogeneous distribution emphasizing the importance to incorporate data from different sources to generate a solid reference set of lncRNAs. KEGG enrichment analysis of host miRNAs putatively targeting lncRNAs upregulated upon feeding showed that these miRNAs are involved in several relevant functions for the tick-host interaction. The possibility that at least some tick lncRNAs act as host miRNA sponges was further explored by identifying lncRNAs with many target regions for a given host miRNA or sets of host miRNAs that consistently target lncRNAs together. Overall, our findings suggest that lncRNAs that may act as sponges have diverse biological roles related to the tick–host interaction in different tissues.

**Keywords:** *Ixodes ricinus*; ectoparasite-host interactions; host immunity; RNA-sequencing; lncRNA
